Composition for repelling and deterring vermin

ABSTRACT

The present invention is directed to a non-therapeutical process for deterring vermin, which is based on the usage of the largely known beta amino-alcohol derivatives of formula (I) 
     
       
         
         
             
             
         
       
     
     as described herein. Further, the present invention is directed to corresponding vermin-deterring compositions which contain these substances as the active ingredient, compounds of the formula (I) for the preparation of vermin-deterring compositions, and the use of compounds of formula (I) in the defense against vermin.

The present invention relates essentially to a non-therapeutical processfor deterring vermin, which is based on the usage of the largely knownbeta amino-alcohol derivatives of formula I shown below. Furthermore, itrelates to corresponding vermin-repelling compositions which containthese substances as the active ingredient, to compounds of formula I forthe preparation of vermin-deterring compositions, and to the use ofcompounds of formula I in the defense against vermin.

It has surprisingly been found that the compounds of formula I below

or their acid addition salts, whereinR1 is hydrogen, halogen, NH₂, OH, C₁-C₃-alkyl or C₁-C₃-alkoxy;m is 1, 2 or 3;R2 is hydrogen, halogen, unsubstituted or substituted benzyl, —C(O)—R8,C₁-C₂₀-alkyl, halo-C₁-C₂₀-alkyl, C₂-C₂₀-alkenylalkyl, C₃-C₅-cycloalkyl,C₁-C₂₀-alkoxyalkyl, C₁-C₂₀-hydroxyalkyl, C₁-C₂₀-alkoxy, unsubstituted orsubstituted arylR3 is a substituent selected from the group consisting of

R4 is hydrogen, C₁-C₂₀-alkoxymethyl, benzyl, —C(O)—R8;n is 0 or 1;R5, R6 and R7 are each independently of each other hydrogen, halogen,unsubstituted or substituted benzyl, C₁-C₂₀-alkyl, halo-C₁-C₂₀-alkyl,C₂-C₂₀-alkenylalkyl, C₃-C₆-cycloalkyl, C₁-C₂₀-alkoxyalkyl,C₁-C₂₀-hydroxyalkyl, C₁-C₂₀-alkoxy, unsubstituted or substituted aryl;andR8 is C₁-C₂₀-alkyl, C₁-C₂₀-alkoxy, unsubstituted or substituted aryl,unsubstituted or substituted aryloxy, benzyl, benzyloxy are eminentlysuitable for deterring vermin. Through the usage according to theinvention of the above compounds, the most varied vermin of humans,animals, objects or certain places can be deterred, whereby numerouscompounds within the scope of formula I are notable for theirparticularly long duration of efficacy.

Compounds of formula I having at least one basic centre may form e.g.acid addition salts. These are formed for example with strong inorganicacids, such as mineral acids, e.g. perchloric acid, sulphuric acid,nitric acid, nitrous acid, a phosphoric acid or a hydrohalic acid, withstrong organic carboxylic acids, typically C₁-C₄alkanecarboxylic acidssubstituted where appropriate for example by halogen, e.g. acetic acid,such as dicarboxylic acids that are unsaturated where appropriate, e.g.oxalic, malonic, succinic, maleic, fumaric or phthalic acid, typicallyhydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric orcitric acid, or benzoic acid, or with organic sulphonic acids, typicallyC₁-C₄alkanesulphonic or arylsulphonic acids substituted whereappropriate for example by halogen, e.g. methanesulphonic orp-toluenesulphonic acid. Of the salts, particular preference is given tothose formed with strong acids, especially with mineral acids, inparticular with the hydrohalic acids HCl and HBr. All multiplesubstitutions are to be interpreted such that identical or differentsubstituents may occur simultaneously.

The alkyl groups present in the definitions of the substituents may bestraight-chained or branched, depending on the number of carbon atoms,and they may be for example methyl, ethyl, propyl, butyl, pentyl, hexyl,heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl,octadecyl, eicosyl, etc. as well as the branched isomers thereof, forexample isopropyl, isobutyl, sec.-butyl, tert.-butyl, isopentyl,neopentyl or isohexyl. Alkoxy, haloalkyl and haloalkoxy radicals arederived from the said alkyl groups.

Halo or halogen normally signifies fluorine, chlorine, bromine oriodine, preferably fluorine or chlorine, especially fluorine, wherebythe corresponding substituent or group may contain one or more identicalor different halogen atoms.

Halogen-substituted carbon-containing groups, such as haloalkyl orhaloalkoxy, may be partially halogenated or perhalogenated, whereby inthe case of multiple halogenation, the halogen substituents may beidentical or different. Examples of haloalkyl—as a group per se and asstructural element of other groups and compounds such as haloalkoxy—aremethyl which is mono- to trisubstituted by fluorine, chlorine and/orbromine, such as CHF₂ or CF₃; ethyl which is mono- to pentasubstitutedby fluorine, chlorine and/or bromine, such as CH₂CF₃, CF₂CF₃, CF₂CCl₃,CF₂CHCl₂, CF₂CHF₂, CF₂CFCl₂, CF₂CHBr₂, CF₂CHClF, CF₂CHBrF or CClFCHClF;propyl or isopropyl, mono- to heptasubstituted by fluorine, chlorineand/or bromine, such as CH₂CHBrCH₂Br, CF₂CHFCF₃, CH₂CF₂CF₃ or CH(CF₃)₂;and butyl or one of its isomers, mono- to nonasubstituted by fluorine,chlorine and/or bromine, such as CF(CF₃)CHFCF₃ or CH₂(CF₂)₂CF₃.

Alkenyl—as a group per se and as structural element of other groups andcompounds such as alkeneoxy, halogenalkenyl or halogenalkeneoxy—is, ineach case with due consideration of the specific number of carbon atomsin the group or compound in question, either straight-chained, forexample vinyl, 1-methylvinyl, allyl, 1-butenyl or 2-hexenyl, orbranched, for example isopropenyl.

Appropriate cycloalkyl substituents contain 3 to 8 carbon atoms and are,for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or cyclooctyl. Corresponding cycloalkenyl substituents maybe mono- or also repeatedly unsaturated, for example cyclopentadienyl orcyclooctatetraenyl. Cyclopentyl and cyclohexyl are preferred.

In the context of the present invention, aryl is understood to be phenylor naphthyl, especially phenyl. These aryl groups are eitherunsubstituted or are substituted once or up to three, in rare cases fourtimes by C₁-C₃-alkyl, C₁-C₃-haloalkyl, C₁-C₃-alkoxy, C₁-C₃-haloalkoxy,halogen, cyano, hydroxyl, amino or nitro, whereby each multiplesubstitution is not limited to identical substituents; instead, mixedsubstituents may appear. Amongst the substituents C₁-C₃-alkyl,C₁-C₃-haloalkyl, C₁-C₃-alkoxy, C₁-C₃-haloalkoxy those with only oneC-atom are most preferred.

Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms.Even more preferred are alkoxy groups having a chain length of 1 to 3carbon atoms. Alkoxy is for example methoxy, ethoxy, propoxy,isopropoxy, n-butoxy, isobutoxy, sec.-butoxy and tert.-butoxy, as wellas the isomers pentyloxy and hexyloxy; preferably methoxy and ethoxy.Haloalkoxy groups preferably have a chain length of 1 to 6 carbon atoms.Haloalkoxy is e.g. fluoro-methoxy, difluoromethoxy, trifluoromethoxy,2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy,2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferablydifluoromethoxy, 2-chloroethoxy and trifluoromethoxy.

Alkoxyalkyl stands for an alkyl group wherein the chain of carbon atomsis preferably once interrupted by an oxygen atom. A hydroxyalkyl is analkyl group carrying preferably one hydroxyl group.

Within the compounds of the formula I the following subgroups ofcompounds are especially preferred due to their pronounced repellingactivity:

A compound of the formula Ia

wherein R1, R2 and R4 have the meanings specified under formula I. Mostpreferred within the formula Ia are compounds wherein R1 is hydrogen;halogen, especially fluorine or chlorine; m is 1 or 2; R2 is hydrogen,C₁-C₃-alkyl, especially methyl; or phenyl; R4 is hydrogen or acetyl.Specific examples of representatives of the formula Ia are provided intable 1 hereinafter. Compounds of the formula Ia are commerciallyavailable, for example from Apollo Chemical Company, LLC; Burlington,N.C., USA.

A compound of the formula Ib

wherein R1, R2, R4 and m have the meanings specified under formula I.Most preferred within the formula Ib are compounds wherein R1 ishydrogen; halogen, especially fluorine or chlorine; m is 1 or 2; R2 ishydrogen, C₁-C₃-alkyl, especially methyl; or phenyl; R4 is hydrogen oracetyl. Specific examples of representatives of the formula Ib areprovided in table 2 hereinafter. Compounds of the formula Ib arecommercially available, for example from Sigma-Aldrich Chemie Gmbh,Munich, Germany or Fluka Chemie AG, Buchs, Switzerland or Chembridge,San Diego, Calif., USA or ABCR GmbH & Co. KG, Karlsruhe, Germany.

A compound of the formula Ic

wherein R1, R2, R4 and m have the meanings specified under formula I.Most preferred within the formula Ib are compounds wherein R1 ishydrogen; halogen, especially fluorine or chlorine; m is 1 or 2; R2 ishydrogen, C₁-C₃-alkyl, especially methyl; or phenyl; R4 is hydrogen oracetyl. Specific examples of representatives of the formula Ic areprovided in table 3 hereinafter. Compounds of the formula Ic arecommercially available, for example from Sigma-Aldrich Chemie Gmbh,Munich, Germany or Fluka Chemie AG, Buchs, Switzerland or ABCR GmbH &Co. KG, Karlsruhe, Germany or Apollo Chemical Company, LLC; Burlington,N.C., USA or Beta Pharma, Inc., New Haven, Conn., USA or OakwoodProducts, Inc., West Columbia, S.C. USA or TCI America, Portland, Oreg.,USA.

A compound of the formula Id

wherein R1, R2, R4 and m have the meanings specified under formula I.Most preferred within the formula Id are compounds wherein R1 ishydrogen; halogen, especially fluorine or chlorine; m is 1 or 2; R2 ishydrogen, C₁-C₃-alkyl, especially methyl; or phenyl; R4 is hydrogen oracetyl. Specific examples of representatives of the formula Id areprovided in table 4 hereinafter. Compounds of the formula Id arecommercially available, for example from Sigma-Aldrich Chemie Gmbh,Munich, Germany or Fluka Chemie AG, Buchs, Switzerland or ABCR GmbH &Co. KG, Karlsruhe, Germany or Apollo Chemical Company, LLC; Burlington,N.C., USA or Beta Pharma, Inc., New Haven, Conn., USA or Acros Organics,Geel, Belgium or Alfa Chemicals Ltd., Binfield, Bracknell, Berkshire, UKor Alfa Aesar GmbH & Co KG, Karlsruhe, Germany.

A compound of the formula Ie

wherein R1, R2, R4 and m have the meanings specified under formula I.Most preferred within the formula Ie are compounds wherein R1 ishydrogen; halogen, especially fluorine or chlorine; m is 1 or 2; R2 ishydrogen, C₁-C₃-alkyl, especially methyl; or phenyl; R4 is hydrogen oracetyl; R5 is hydrogen, R6 is hydrogen or phenyl; and R7 is hydrogen,C₁-C₃-alkyl, especially methyl; or benzyl. Specific examples ofrepresentatives of the formula Ie are provided in table 5 hereinafter.Compounds of the formula Ie are commercially available, for example fromSigma-Aldrich Chemie Gmbh, Munich, Germany or ABCR GmbH & Co. KG,Karlsruhe, Germany or Alfa Chemicals Ltd., Binfield, Bracknell,Berkshire, UK or or TCI America, Portland, Oreg., USA or BioNEt,Newcastle University, NE2 4HH, UK.

Any of the compounds selected from the following group constitutes amost preferred embodiment of the present invention: Acetic acid2-dibenzylamino-ethyl ester; Dibenzylamino-ethanol; 2-Propyl-pentanoicacid 2-dibenzylamino-ethyl ester; 1-Benzyl-pyrrolidin-3-ol; Acetic acid1-benzyl-pyrrolidin-3-yl ester; 2,2-Dimethyl-propionic acid1-benzyl-pyrrolidin-3-yl ester; Benzoic acid 1-benzyl-pyrrolidin-3-ylester; (1-Benzyl-pyrrolidin-2-yl)-methanol; 1-Benzyl-piperidin-3-ol;(1-Benzyl-piperidin-2-yl)-methanol; 2-(Benzyl-methyl-amino)-ethanol;2-Dibenzylamino-propan-1-ol; 2-Benzylamino-ethanol; and2-Benzylamino-1-phenyl-ethanol.

The majority of the compounds of the present invention is commerciallyavailable or can be produced in the same way as the commerciallyavailable representatives. The compounds of the present invention can beproduced by a variety of methods, for example, as shown in Scheme 1below. Thus an amino-alcohol with a protected hydroxyl group may reactwith a benzylic carbon activated by a chlorine, bromine, iodine atom oralternatively by any other leaving groups such as tosylate, mesylate ortriflate. This reaction may or not require the presence of a base (e.g.tertiary amines such as triethylamine, diisopropylethylamine), it can becarried out at a temperature of between 0° C. and 100° C. in an organicsolvent such as THF, dichloromethane. The protective group can beremoved using well known conditions (Protective Groups in OrganicSynthesis, T. W. Greene/P. G. M. Wuts, Wiley Interscience).

Prodrugs (ester, alkyloxymethyl derivatives) of the free hydroxymolecule can be synthesized by reacting the hydroxyl group withalkyloxymethylchlorid to generate acetals or by classical esterificationbetween the hydroxyl group and a carboxylic acid or its correspondingacid chloride.

For the compounds of formula Id another syntheses may be used asdescribed in Scheme 2. They enable quick access to unsubstituted orsubstituted beta aminoalcohol from the corresponding secondary amine.Benzylamines can react with ethylcarbonate to generate the correspondingunsubstituted amino alcohol without use of any solvent but presence oftetrabutylammonium iodide. The substituted amino alcohol are prepared bynucleophilic attack of nitrogen atom on hydroxyl-protected ethanolsubstituted by a leaving group X. The reaction is classically run in THFor similar organic solvent with a base (e.g. tertiary amines such astriethylamine, diisopropylethylamine).

As mentioned previously for scheme 1 prodrugs (ester, alkyloxymethylderivatives) of the free hydroxy molecule can be synthesized by reactingthe hydroxyl group with alkyloxymethylchlorid to generate acetals or byclassical esterification between the hydroxyl group and a carboxylicacid or its corresponding acid chloride.

The compounds of formula I may be in the form of one of the possibleisomers or in the form of a mixture thereof, for example depending uponthe number of asymmetric carbon atoms and the absolute and relativeconfiguration thereof, in the form of pure isomers or in the form ofmixtures of isomers, such as mixtures of enantiomers or mixtures ofdiastereoisomers. The invention relates both to the pure isomers and toall possible mixtures of isomers and this is to be understoodaccordingly hereinbefore and hereinafter, even when stereochemicaldetails are not specifically mentioned in each case.

Mixtures of diastereoisomers and mixtures of racemates of compounds offormula I obtainable in accordance with the process—depending upon thestarting materials and procedures chosen—or by other means can beseparated into the pure diastereoisomers or racemates in known manner onthe basis of the physico-chemical differences between the constituents,for example by fractional crystallisation, distillation and/orchromatography. Mixtures of enantiomers or racemates so obtainable canbe separated into the optical antipodes by known methods, for example byrecrystallisation from an optically active solvent, by chromatography onchiral adsorbents, for example high-pressure liquid chromatography(HPLC) on acetyl cellulose, with the aid of suitable microorganisms, bycleavage with specific immobilised enzymes, or via the formation ofinclusion compounds, for example using chiral crown ethers, in whichcase only one enantiomer is complexed. Pure diastereoisomers andenantiomers can be obtained not only by separation of correspondingmixtures of isomers but also, according to the invention, by generallyknown methods of diastereoselective or enantioselective synthesis, forexample by carrying out the process according to the invention withstarting materials that have appropriate stereo-chemistry.

In the context of the present invention, vermin are understood to be inparticular insects, mites and ticks. These include insects of the order:Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera,Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera,Psocoptera and Hymenoptera. However, the vermin which may be mentionedin particular are those which trouble humans or animals and carrypathogens, for example flies such as Musca domestica, Muscavetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria,Lucilia cuprina, Hypoderma bovis, Hypoderma lineatum, Chrysomyiachloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilusintestinalis, Oestrus ovis, Stomoxys calcitrans, Haematobia irritans andmidges (Nematocera), such as Culicidae, Simuliidae, Psychodidae, butalso blood-sucking vermin, for example fleas, such as Ctenocephalidesfells and Ctenocephalides canis (cat and dog fleas), Xenopsylla cheopis,Pulex irritans, Dermatophilus penetrans, lice, such as Damalina ovis,Pediculus humanis, biting flies and horse-flies (Tabanidae), Haematopotaspp. such as Haematopota pluvialis, Tabanidea spp. such as Tabanusnigrovittatus, Chrysopsinae spp. such as Chrysops caecutiens, tsetseflies, such as species of Glossinia, biting insects, particularlycockroaches, such as Blatella germanica, Blatta orientalis, Periplanetaamericana, mites, such as Dermanyssus gallinae, Sarcoptes scabiei,Psoroptes ovis and Psorergates spp. and last but not least ticks. Thelatter belong to the order Acarina. Known representatives of ticks are,for example, Boophilus, Amblyomma, Anocentor, Dermacentor,Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus,Argas, Otobius and Ornithodoros and the like, which preferably infestwarm-blooded animals including farm animals, such as cattle, pigs, sheepand goats, poultry such as chickens, turkeys and geese, fur-bearinganimals such as mink, foxes, chinchillas, rabbits and the like, as wellas domestic animals such as cats and dogs, but also humans.

Ticks may be divided into hard and soft ticks, and are characterised byinfesting one, two or three host animals. They attach themselves to apassing host animal and suck the blood or body fluids. Fully engorgedfemale ticks drop from the host animal and lay large amounts of eggs(2000 to 3000) in a suitable crack in the floor or in any otherprotected site where the larvae hatch. These in turn seek a host animal,in order to suck blood from it. Larvae of ticks which only infest onehost animal moult twice and thus become nymphs and finally adult tickswithout leaving the host they have selected. Larvae of ticks whichinfest two or three host animals leave the animal after feeding on theblood, moult in the local environment and seek a second or third host asnymphs or as adult ticks, in order to suck its blood. Ticks areresponsible world-wide for the transmission and spread of many human andanimal diseases. Because of their economic influence, the most importantticks are Boophilus, Rhipicephalus, Ixodes, Hyalomma, Amblyomma andDermacentor. They are carriers of bacterial, viral, rickettsial andprotozoal diseases and cause tick-paralysis and tick-toxicosis. Even asingle tick can cause paralysis whereby its saliva penetrates into thehost animal during ingestion. Diseases caused by ticks are usuallytransmitted by ticks, which infest several host animals. Such diseases,for example babesiosis, anaplasmosis, theileriasis and heart waterdisease, are responsible for the death or impairment of a large numberof domestic and farm animals in the entire world. In many countries oftemperate climate, Ixodide ticks transmit the agent of the chronicallyharmful Lyme's disease from wild animals to humans. Apart from thetransmission of disease, the ticks are responsible for great economiclosses in livestock production. Losses are not confined to the death ofthe host animals, but also include damage to the pelts, loss of growth,a reduction in milk production and reduced value of the meat. Althoughthe harmful effects of a tick infestation on animals have been known foryears, and enormous progress has been made using tick-controlprogrammes, until now no completely satisfactory methods of controllingor eliminating these parasites have been found, and in addition, tickshave often developed resistance to chemical active ingredients.

The infestation of fleas on domestic animals and pets likewise stillrepresents for the owner a problem which has not been satisfactorilyresolved or can only be resolved at considerable expense. As with ticks,fleas are not only troublesome, but are carriers of disease, andtransmit various fungal diseases from host animal to host animal and tothe animal keeper, particularly in moist, warm climatic areas, forexample in the Mediterranean, in the southern part of USA, etc. Those atrisk in particular are people with a weakened immune system or childrenwhose immune system has not yet fully developed. Owing to their complexlife cycle, none of the known methods for the control of fleas iscompletely satisfactory, especially as most known methods are basicallydirected towards the control of adult fleas in the pelt, and leavecompletely untouched the different juvenile stages of the fleas, whichexist not only in the pelt of the animal, but also on the floor, incarpets, in the bedding of the animal, on chairs, in the garden and allother places with which the infested animal comes into contact. Fleatreatment is usually expensive and has to be continued over long periodsof time. Success usually depends on treating not only the infestedanimal, e.g. the dog or cat, but at the same time all the locationswhich the infested animal frequents.

Such a complicated procedure is unnecessary with the present compoundsof formula (I), since a particular advantage of the compounds of formulaI under discussion is that they are extremely effective and at the sametime of very low toxicity both for the target parasites and for thewarm-blooded animals. This is because their activity is based not on thedeath of the target parasite, but on the parrying defence thereof,before it attacks, sting, bites or in any other way harms the hostorganism. The presence of the compounds of formula I being discussedhere appears to disturb the parasites in such a way that they suddenlyleave the treated environment without biting or stinging, or even do notinfest a treated host animal at all. What is striking is that the effectsets in when the parasite comes into contact with the active ingredientfor a short time. After contact for a short time, the parasite avoidsany further contact with the active ingredient. An additional advantagelies in the long-term action, e.g. compared with DEET(N,N-diethyl-m-toluamide), which although very effective, volatilizesrather rapidly and therefore has to be reapplied already after ca. 2hours, and is thus not appropriate for the long-term treatment ofanimals. Usage of the present active ingredients is also pleasantbecause they are almost odorless.

Although the present active ingredients can of course be mixed withother substances having the same sphere of activity or withparasiticides or with other activity-improving substances to achievefurther improved or longer-lasting action, and then applied, in contrastto many compounds of the prior art, this is totally unnecessary, as theyalready combine all the advantageous properties.

If the parasite is not only to be kept at bay, but also killed, ofcourse this can be achieved by adding appropriate insecticides and/oracaricides. In practice, however, this is unnecessary in most cases.

The present active ingredients are preferably used in diluted form.Normally, they are brought to the final application form by usingappropriate formulation excipients, and they then contain between 0.1and 95% by weight, preferably 0.5 to 90% by weight of the activeingredient.

Since the active ingredients are in many instances applied towarm-blooded animals and of course come into contact with the skin,suitable formulation excipients are the excipients and administrationforms that are known in cosmetics. They may be administered in the formof solutions, emulsions, ointments, creams, pastes, powders, sprays,etc.

For administration to farm animals or pets, such as cows, horses, asses,camels, dogs, cats, poultry, sheep, goats, etc., the so-called ‘pour-on’or ‘spot-on’ formulations are especially suitable; these liquid orsemi-liquid formulations have the advantage that they only have to beapplied to a small area of the pelt or plumage, and, thanks to theproportion of spreading oils or other spreading additives, they disperseby themselves over the whole pelt or plumage, without having to doanything else, and become active over the whole area.

Of course, inanimate materials, for example clothing or dog and catbaskets, stables, carpets, curtains, living quarters, conservatories,etc. may be treated with said formulations and thus protected fromparasite infestation.

To control cockroaches, their locus, usually cracks in the walls,furniture, etc., can be sprayed or powdered. Since cockroaches areextremely vigorous and it is almost impossible to drive them awaycompletely, it is recommended that when using the present activeingredients, insecticides having activity against cockroaches are usedadditionally.

For application on humans, a pleasant-smelling essence, e.g. a perfume,can be added to make application more attractive.

The following examples of preparation and usage of the activeingredients according to the invention serve to illustrate the inventionwithout restricting it.

In particular, preferred formulations are made up as follows:

FORMULATION EXAMPLE 1

A vermin-deterring composition in the form of a lotion for applicationto the skin is prepared by mixing 30 parts of one of the activeingredients according to the invention selected from the compoundslisted in one of the tables 1 to 5, 1.5 parts of perfume and 68.5 partsof isopropanol, whereby the latter may be replaced by ethanol.

FORMULATION EXAMPLE 2

A vermin-deterring composition in the form of an aerosol for sprayingonto the pelt of a pet is prepared by formulating 50% active ingredientsolution, consisting of 30 parts of one of the active ingredientsaccording to the invention selected from the compounds listed in one ofthe tables 1 to 5, 1.5 parts of perfume and 68.5 parts of isopropanol,with 50% Frigen 11/12 (a halogenated hydrocarbon) as propellant gas inan aerosol can.

FORMULATION EXAMPLE 3

A vermin-deterring composition in the form of an aerosol for sprayingonto the skin is prepared by formulating 40% active ingredient solution,consisting of 20 parts of one of the active ingredients according to theinvention selected from the compounds listed in one of the tables 1 to5, 1 part of perfume, 79 parts of isopropanol, with 60% propane/butane(in a ratio of 15:85) as propellant gas in an aerosol can.

PREPARATION EXAMPLE Preparation Acetic Acid 2-dibenzylamino-ethyl ester

Step 1: 0.5 gram of dibenzylamine (2.5 mmol), 0.446 gram ofethylenecarbonate (5 mmol) and 0.215 gram of tetraethylammoniumiodide(083 mmol) were mixed together at room temperature. The solid mixturewas then heated at 140° C. and the resulting suspension was stirred atthis temperature for 26 hours. The reaction mixture was diluted withethyl acetate and extracted with 10 mL of a 0.5M solution of sodiumhydroxide. The aqueous phase was washed with ethyl acetate and thecombined organic phases were washed twice with brine. The organic phasewas dried on magnesium sulfate, filtered, concentrated under reducedpressure and purified by flash chromatography on silica gel (eluant:ethylacetate/hexane 1/2) to afford 0.5 gram ofN,N-dibenzyl-2-aminoethanol (yield: 83%) as an oil.

Step 2: 18.5 grams (76.6 mmol) of N,N-dibenzyl-2-aminoethanol arediluted in dichloromethane (350 mL) at room temperature followed by theaddition of N,N-diisopropylethylamine (16.47 mL, 99.7 mmol) and4-dimethylaminopyridine (0.937 grams). The reaction is stirred for 15minutes at 10° C. and 5.2 mL (92 mmol) of acetylchloride are addeddropwise at 0° C. over 20 minutes. The reaction mixture is then stirredfor 30 minutes at 0° C. and 20 hours at room temperature before theaddition of 200 mL of a saturated aqueous solution of sodiumbicarbonate. The organic phase is extracted, washed with brine, driedover magnesium sulfate, filtered and concentrated under reduced pressureto afford 23.48 grams of a yellowish oil. The oil is purified by flashchromatography on silica gel (eluant: ethylacetate/hexane 1/9) to afford18.2 grams of title product as a colorless oil (83% yield).

The following tables exemplify compounds that can be used in accordancewith the teaching of the present invention but do not limit it to thesesspecific examples.

TABLE 1 Non-limiting examples of compounds of the formula Ia (Ia)

Compound No. —(R1)m R2 R4 1.001 H H H 1.002 2-F H H 1.003 3-F H H 1.0044-F H H 1.005 2-Cl H H 1.006 3-Cl H H 1.007 4-Cl H H 1.008 2,4-di-F H H1.009 3,4-di-F H H 1.010 2,3-di-F H H 1.011 2,5-di-F H H 1.012 2,6-di-FH H 1.013 3,5-di-F H H 1.014 H Me H 1.015 2-F Me H 1.016 3-F Me H 1.0174-F Me H 1.018 2-Cl Me H 1.019 3-Cl Me H 1.020 4-Cl Me H 1.021 2,4-di-FMe H 1.022 3,4-di-F Me H 1.023 2,3-di-F Me H 1.024 2,5-di-F Me H 1.0252,6-di-F Me H 1.026 3,5-di-F Me H 1.027 H Phenyl H 1.028 2-F Phenyl H1.029 3-F Phenyl H 1.030 4-F Phenyl H 1.031 2-Cl Phenyl H 1.032 3-ClPhenyl H 1.033 4-Cl Phenyl H 1.034 2,4-di-F Phenyl H 1.035 3,4-di-FPhenyl H 1.036 2,3-di-F Phenyl H 1.037 2,5-di-F Phenyl H 1.038 2,6-di-FPhenyl H 1.039 3,5-di-F Phenyl H 1.040 H H Me—C(O)— 1.041 2-F H Me—C(O)—1.042 3-F H Me—C(O)— 1.043 4-F H Me—C(O)— 1.044 2-Cl H Me—C(O)— 1.0453-Cl H Me—C(O)— 1.046 4-Cl H Me—C(O)— 1.047 2,4-di-F H Me—C(O)— 1.0483,4-di-F H Me—C(O)— 1.049 2,3-di-F H Me—C(O)— 1.050 2,5-di-F H Me—C(O)—1.051 2,6-di-F H Me—C(O)— 1.052 3,5-di-F H Me—C(O)— 1.053 H Me Me—C(O)—1.054 2-F Me Me—C(O)— 1.055 3-F Me Me—C(O)— 1.056 4-F Me Me—C(O)— 1.0572-Cl Me Me—C(O)— 1.058 3-Cl Me Me—C(O)— 1.059 4-Cl Me Me—C(O)— 1.0602,4-di-F Me Me—C(O)— 1.061 3,4-di-F Me Me—C(O)— 1.062 2,3-di-F MeMe—C(O)— 1.063 2,5-di-F Me Me—C(O)— 1.064 2,6-di-F Me Me—C(O)— 1.0653,5-di-F Me Me—C(O)— 1.066 H Phenyl Me—C(O)— 1.067 2-F Phenyl Me—C(O)—1.068 3-F Phenyl Me—C(O)— 1.069 4-F Phenyl Me—C(O)— 1.070 2-Cl PhenylMe—C(O)— 1.071 3-Cl Phenyl Me—C(O)— 1.072 4-Cl Phenyl Me—C(O)— 1.0732,4-di-F Phenyl Me—C(O)— 1.074 3,4-di-F Phenyl Me—C(O)— 1.075 2,3-di-FPhenyl Me—C(O)— 1.076 2,5-di-F Phenyl Me—C(O)— 1.077 2,6-di-F PhenylMe—C(O)— 1.078 3,5-di-F Phenyl Me—C(O)—

TABLE 2 Non-limiting examples of compounds of the formula Ib (Ib)

Compound No. —(R1)m R2 R4 2.001 H H H 2.002 2-F H H 2.003 3-F H H 2.0044-F H H 2.005 2-Cl H H 2.006 3-Cl H H 2.007 4-Cl H H 2.008 2,4-di-F H H2.009 3,4-di-F H H 2.010 2,3-di-F H H 2.011 2,5-di-F H H 2.012 2,6-di-FH H 2.013 3,5-di-F H H 2.014 H Me H 2.015 2-F Me H 2.016 3-F Me H 2.0174-F Me H 2.018 2-Cl Me H 2.019 3-Cl Me H 2.020 4-Cl Me H 2.021 2,4-di-FMe H 2.022 3,4-di-F Me H 2.023 2,3-di-F Me H 2.024 2,5-di-F Me H 2.0252,6-di-F Me H 2.026 3,5-di-F Me H 2.027 H Phenyl H 2.028 2-F Phenyl H2.029 3-F Phenyl H 2.030 4-F Phenyl H 2.031 2-Cl Phenyl H 2.032 3-ClPhenyl H 2.033 4-Cl Phenyl H 2.034 2,4-di-F Phenyl H 2.035 3,4-di-FPhenyl H 2.036 2,3-di-F Phenyl H 2.037 2,5-di-F Phenyl H 2.038 2,6-di-FPhenyl H 2.039 3,5-di-F Phenyl H 2.040 H H Me—C(O)— 2.041 2-F H Me—C(O)—2.042 3-F H Me—C(O)— 2.043 4-F H Me—C(O)— 2.044 2-Cl H Me—C(O)— 2.0453-Cl H Me—C(O)— 2.046 4-Cl H Me—C(O)— 2.047 2,4-di-F H Me—C(O)— 2.0483,4-di-F H Me—C(O)— 2.049 2,3-di-F H Me—C(O)— 2.050 2,5-di-F H Me—C(O)—2.051 2,6-di-F H Me—C(O)— 2.052 3,5-di-F H Me—C(O)— 2.053 H Me Me—C(O)—2.054 2-F Me Me—C(O)— 2.055 3-F Me Me—C(O)— 2.056 4-F Me Me—C(O)— 2.0572-Cl Me Me—C(O)— 2.058 3-Cl Me Me—C(O)— 2.059 4-Cl Me Me—C(O)— 2.0602,4-di-F Me Me—C(O)— 2.061 3,4-di-F Me Me—C(O)— 2.062 2,3-di-F MeMe—C(O)— 2.063 2,5-di-F Me Me—C(O)— 2.064 2,6-di-F Me Me—C(O)— 2.0653,5-di-F Me Me—C(O)— 2.066 H Phenyl Me—C(O)— 2.067 2-F Phenyl Me—C(O)—2.068 3-F Phenyl Me—C(O)— 2.069 4-F Phenyl Me—C(O)— 2.070 2-Cl PhenylMe—C(O)— 2.071 3-Cl Phenyl Me—C(O)— 2.072 4-Cl Phenyl Me—C(O)— 2.0732,4-di-F Phenyl Me—C(O)— 2.074 3,4-di-F Phenyl Me—C(O)— 2.075 2,3-di-FPhenyl Me—C(O)— 2.076 2,5-di-F Phenyl Me—C(O)— 2.077 2,6-di-F PhenylMe—C(O)— 2.078 3,5-di-F Phenyl Me—C(O)—

TABLE 3 Non-limiting examples of compounds of the formula Ic (Ic)

Compound No. —(R1)m R2 R4 3.001 H H H 3.002 2-F H H 3.003 3-F H H 3.0044-F H H 3.005 2-Cl H H 3.006 3-Cl H H 3.007 4-Cl H H 3.008 2,4-di-F H H3.009 3,4-di-F H H 3.010 2,3-di-F H H 3.011 2,5-di-F H H 3.012 2,6-di-FH H 3.013 3,5-di-F H H 3.014 H Me H 3.015 2-F Me H 3.016 3-F Me H 3.0174-F Me H 3.018 2-Cl Me H 3.019 3-Cl Me H 3.020 4-Cl Me H 3.021 2,4-di-FMe H 3.022 3,4-di-F Me H 3.023 2,3-di-F Me H 3.024 2,5-di-F Me H 3.0252,6-di-F Me H 3.026 3,5-di-F Me H 3.027 H Phenyl H 3.028 2-F Phenyl H3.029 3-F Phenyl H 3.030 4-F Phenyl H 3.031 2-Cl Phenyl H 3.032 3-ClPhenyl H 3.033 4-Cl Phenyl H 3.034 2,4-di-F Phenyl H 3.035 3,4-di-FPhenyl H 3.036 2,3-di-F Phenyl H 3.037 2,5-di-F Phenyl H 3.038 2,6-di-FPhenyl H 3.039 3,5-di-F Phenyl H 3.040 H H (Oil) Me—C(O)— 3.041 2-F HMe—C(O)— 3.042 3-F H Me—C(O)— 3.043 4-F H Me—C(O)— 3.044 2-Cl H Me—C(O)—3.045 3-Cl H Me—C(O)— 3.046 4-Cl H Me—C(O)— 3.047 2,4-di-F H Me—C(O)—3.048 3,4-di-F H Me—C(O)— 3.049 2,3-di-F H Me—C(O)— 3.050 2,5-di-F HMe—C(O)— 3.051 2,6-di-F H Me—C(O)— 3.052 3,5-di-F H Me—C(O)— 3.053 H MeMe—C(O)— 3.054 2-F Me Me—C(O)— 3.055 3-F Me Me—C(O)— 3.056 4-F MeMe—C(O)— 3.057 2-Cl Me Me—C(O)— 3.058 3-Cl Me Me—C(O)— 3.059 4-Cl MeMe—C(O)— 3.060 2,4-di-F Me Me—C(O)— 3.061 3,4-di-F Me Me—C(O)— 3.0622,3-di-F Me Me—C(O)— 3.063 2,5-di-F Me Me—C(O)— 3.064 2,6-di-F MeMe—C(O)— 3.065 3,5-di-F Me Me—C(O)— 3.066 H Phenyl Me—C(O)— 3.067 2-FPhenyl Me—C(O)— 3.068 3-F Phenyl Me—C(O)— 3.069 4-F Phenyl Me—C(O)—3.070 2-Cl Phenyl Me—C(O)— 3.071 3-Cl Phenyl Me—C(O)— 3.072 4-Cl PhenylMe—C(O)— 3.073 2,4-di-F Phenyl Me—C(O)— 3.074 3,4-di-F Phenyl Me—C(O)—3.075 2,3-di-F Phenyl Me—C(O)— 3.076 2,5-di-F Phenyl Me—C(O)— 3.0772,6-di-F Phenyl Me—C(O)— 3.078 3,5-di-F Phenyl Me—C(O)— 3.079 H H (Oil)Phe—C(O)— 3.080 H H (Oil) (CH₃)₃C—C(O)—

TABLE 4 Non-limiting examples of compounds of the formula Id (Id)

Compound No. —(R1)m R2 R4 4.001 H H H 4.002 2-F H H 4.003 3-F H H 4.0044-F H H 4.005 2-Cl H H 4.006 3-Cl H H 4.007 4-Cl H H 4.008 2,4-di-F H H4.009 3,4-di-F H H 4.010 2,3-di-F H H 4.011 2,5-di-F H H 4.012 2,6-di-FH H 4.013 3,5-di-F H H 4.014 H Me H 4.015 2-F Me H 4.016 3-F Me H 4.0174-F Me H 4.018 2-Cl Me H 4.019 3-Cl Me H 4.020 4-Cl Me H 4.021 2,4-di-FMe H 4.022 3,4-di-F Me H 4.023 2,3-di-F Me H 4.024 2,5-di-F Me H 4.0252,6-di-F Me H 4.026 3,5-di-F Me H 4.027 H Phenyl H 4.028 2-F Phenyl H4.029 3-F Phenyl H 4.030 4-F Phenyl H 4.031 2-Cl Phenyl H 4.032 3-ClPhenyl H 4.033 4-Cl Phenyl H 4.034 2,4-di-F Phenyl H 4.035 3,4-di-FPhenyl H 4.036 2,3-di-F Phenyl H 4.037 2,5-di-F Phenyl H 4.038 2,6-di-FPhenyl H 4.039 3,5-di-F Phenyl H 4.040 H H Me—C(O)— 4.041 2-F H Me—C(O)—4.042 3-F H Me—C(O)— 4.043 4-F H Me—C(O)— 4.044 2-Cl H Me—C(O)— 4.0453-Cl H Me—C(O)— 4.046 4-Cl H Me—C(O)— 4.047 2,4-di-F H Me—C(O)— 4.0483,4-di-F H Me—C(O)— 4.049 2,3-di-F H Me—C(O)— 4.050 2,5-di-F H Me—C(O)—4.051 2,6-di-F H Me—C(O)— 4.052 3,5-di-F Me Me—C(O)— 4.053 H Me Me—C(O)—4.054 2-F Me Me—C(O)— 4.055 3-F Me Me—C(O)— 4.056 4-F Me Me—C(O)— 4.0572-Cl Me Me—C(O)— 4.058 3-Cl Me Me—C(O)— 4.059 4-Cl Me Me—C(O)— 4.0602,4-di-F Me Me—C(O)— 4.061 3,4-di-F Me Me—C(O)— 4.062 2,3-di-F MeMe—C(O)— 4.063 2,5-di-F Me Me—C(O)— 4.064 2,6-di-F Me Me—C(O)— 4.0653,5-di-F Phenyl Me—C(O)— 4.066 H Phenyl Me—C(O)— 4.067 2-F PhenylMe—C(O)— 4.068 3-F Phenyl Me—C(O)— 4.069 4-F Phenyl Me—C(O)— 4.070 2-ClPhenyl Me—C(O)— 4.071 3-Cl Phenyl Me—C(O)— 4.072 4-Cl Phenyl Me—C(O)—4.073 2,4-di-F Phenyl Me—C(O)— 4.074 3,4-di-F Phenyl Me—C(O)— 4.0752,3-di-F Phenyl Me—C(O)— 4.076 2,5-di-F Phenyl Me—C(O)— 4.077 2,6-di-FPhenyl Me—C(O)— 4.078 3,5-di-F Phenyl Me—C(O)—

TABLE 5 Non-limiting examples of compounds of the formula Ie (Ie)

No. —(R1)m R2 R4 R5 R6 R7 5.001 H H H H H Benzyl 5.002 2-F H H H HBenzyl 5.003 3-F H H H H Benzyl 5.004 4-F H H H H Benzyl 5.005 2-Cl H HH H Benzyl 5.006 3-Cl H H H H Benzyl 5.007 4-Cl H H H H Benzyl 5.0082,4-di-F H H H H Benzyl 5.009 3,4-di-F H H H H Benzyl 5.010 2,3-di-F H HH H Benzyl 5.011 2,5-di-F H H H H Benzyl 5.012 2,6-di-F H H H H Benzyl5.013 3,5-di-F H H H H Benzyl 5.014 H Me H H H Benzyl 5.015 2-F Me H H HBenzyl 5.016 3-F Me H H H Benzyl 5.017 4-F Me H H H Benzyl 5.018 2-Cl MeH H H Benzyl 5.019 3-Cl Me H H H Benzyl 5.020 4-Cl Me H H H Benzyl 5.0212,4-di-F Me H H H Benzyl 5.022 3,4-di-F Me H H H Benzyl 5.023 2,3-di-FMe H H H Benzyl 5.024 2,5-di-F Me H H H Benzyl 5.025 2,6-di-F Me H H HBenzyl 5.026 3,5-di-F Me H H H Benzyl 5.027 H Phenyl H H H Benzyl 5.0282-F Phenyl H H H Benzyl 5.029 3-F Phenyl H H H Benzyl 5.030 4-F Phenyl HH H Benzyl 5.031 2-Cl Phenyl H H H Benzyl 5.032 3-Cl Phenyl H H H Benzyl5.033 4-Cl Phenyl H H H Benzyl 5.034 2,4-di-F Phenyl H H H Benzyl 5.0353,4-di-F Phenyl H H H Benzyl 5.036 2,3-di-F Phenyl H H H Benzyl 5.0372,5-di-F Phenyl H H H Benzyl 5.038 2,6-di-F Phenyl H H H Benzyl 5.0393,5-di-F Phenyl H H H Benzyl 5.040 H H Me—C(O)— H H Benzyl (Oil) 5.0412-F H Me—C(O)— H H Benzyl 5.042 3-F H Me—C(O)— H H Benzyl 5.043 4-F HMe—C(O)— H H Benzyl 5.044 2-Cl H Me—C(O)— H H Benzyl 5.045 3-Cl HMe—C(O)— H H Benzyl 5.046 4-Cl H Me—C(O)— H H Benzyl 5.047 2,4-di-F HMe—C(O)— H H Benzyl 5.048 3,4-di-F H Me—C(O)— H H Benzyl 5.049 2,3-di-FH Me—C(O)— H H Benzyl 5.050 2,5-di-F H Me—C(O)— H H Benzyl 5.0512,6-di-F H Me—C(O)— H H Benzyl 5.052 3,5-di-F H Me—C(O)— H H Benzyl5.053 H Me Me—C(O)— H H Benzyl 5.054 2-F Me Me—C(O)— H H Benzyl 5.0553-F Me Me—C(O)— H H Benzyl 5.056 4-F Me Me—C(O)— H H Benzyl 5.057 2-ClMe Me—C(O)— H H Benzyl 5.058 3-Cl Me Me—C(O)— H H Benzyl 5.059 4-Cl MeMe—C(O)— H H Benzyl 5.060 2,4-di-F Me Me—C(O)— H H Benzyl 5.061 3,4-di-FMe Me—C(O)— H H Benzyl 5.062 2,3-di-F Me Me—C(O)— H H Benzyl 5.0632,5-di-F Me Me—C(O)— H H Benzyl 5.064 2,6-di-F Me Me—C(O)— H H Benzyl5.065 3,5-di-F Me Me—C(O)— H H Benzyl 5.066 H Phenyl Me—C(O)— H H Benzyl5.067 2-F Phenyl Me—C(O)— H H Benzyl 5.068 3-F Phenyl Me—C(O)— H HBenzyl 5.069 4-F Phenyl Me—C(O)— H H Benzyl 5.070 2-Cl Phenyl Me—C(O)— HH Benzyl 5.071 3-Cl Phenyl Me—C(O)— H H Benzyl 5.072 4-Cl PhenylMe—C(O)— H H Benzyl 5.073 2,4-di-F Phenyl Me—C(O)— H H Benzyl 5.0743,4-di-F Phenyl Me—C(O)— H H Benzyl 5.075 2,3-di-F Phenyl Me—C(O)— H HBenzyl 5.076 2,5-di-F Phenyl Me—C(O)— H H Benzyl 5.077 2,6-di-F PhenylMe—C(O)— H H Benzyl 5.078 3,5-di-F Phenyl Me—C(O)— H H Benzyl 5.079 H HH H Phenyl H 5.080 2-F H H H Phenyl H 5.081 3-F H H H Phenyl H 5.082 4-FH H H Phenyl H 5.083 2-Cl H H H Phenyl H 5.084 3-Cl H H H Phenyl H 5.0854-Cl H H H Phenyl H 5.086 2,4-di-F H H H Phenyl H 5.087 3,4-di-F H H HPhenyl H 5.088 2,3-di-F H H H Phenyl H 5.089 2,5-di-F H H H Phenyl H5.090 2,6-di-F H H H Phenyl H 5.091 3,5-di-F H H H Phenyl H 5.092 H Me HH Phenyl H 5.093 2-F Me H H Phenyl H 5.094 3-F Me H H Phenyl H 5.095 4-FMe H H Phenyl H 5.096 2-Cl Me H H Phenyl H 5.097 3-Cl Me H H Phenyl H5.098 4-Cl Me H H Phenyl H 5.099 2,4-di-F Me H H Phenyl H 5.100 3,4-di-FMe H H Phenyl H 5.101 2,3-di-F Me H H Phenyl H 5.102 2,5-di-F Me H HPhenyl H 5.103 2,6-di-F Me H H Phenyl H 5.104 3,5-di-F Me H H Phenyl H5.105 H Phenyl H H Phenyl H 5.106 2-F Phenyl H H Phenyl H 5.107 3-FPhenyl H H Phenyl H 5.108 4-F Phenyl H H Phenyl H 5.109 2-Cl Phenyl H HPhenyl H 5.110 3-Cl Phenyl H H Phenyl H 5.111 4-Cl Phenyl H H Phenyl H5.112 2,4-di-F Phenyl H H Phenyl H 5.113 3,4-di-F Phenyl H H Phenyl H5.114 2,3-di-F Phenyl H H Phenyl H 5.115 2,5-di-F Phenyl H H Phenyl H5.116 2,6-di-F Phenyl H H Phenyl H 5.117 3,5-di-F Phenyl H H Phenyl H5.118 H H Me—C(O)— H Phenyl H 5.119 2-F H Me—C(O)— H Phenyl H 5.120 3-FH Me—C(O)— H Phenyl H 5.121 4-F H Me—C(O)— H Phenyl H 5.122 2-Cl HMe—C(O)— H Phenyl H 5.123 3-Cl H Me—C(O)— H Phenyl H 5.124 4-Cl HMe—C(O)— H Phenyl H 5.125 2,4-di-F H Me—C(O)— H Phenyl H 5.126 3,4-di-FH Me—C(O)— H Phenyl H 5.127 2,3-di-F H Me—C(O)— H Phenyl H 5.1282,5-di-F H Me—C(O)— H Phenyl H 5.129 2,6-di-F H Me—C(O)— H Phenyl H5.130 3,5-di-F H Me—C(O)— H Phenyl H 5.131 H Me Me—C(O)— H Phenyl H5.132 2-F Me Me—C(O)— H Phenyl H 5.133 3-F Me Me—C(O)— H Phenyl H 5.1344-F Me Me—C(O)— H Phenyl H 5.135 2-Cl Me Me—C(O)— H Phenyl H 5.136 3-ClMe Me—C(O)— H Phenyl H 5.137 4-Cl Me Me—C(O)— H Phenyl H 5.138 2,4-di-FMe Me—C(O)— H Phenyl H 5.139 3,4-di-F Me Me—C(O)— H Phenyl H 5.1402,3-di-F Me Me—C(O)— H Phenyl H 5.141 2,5-di-F Me Me—C(O)— H Phenyl H5.142 2,6-di-F Me Me—C(O)— H Phenyl H 5.143 3,5-di-F Me Me—C(O)— HPhenyl H 5.144 H Phenyl Me—C(O)— H Phenyl H 5.145 2-F Phenyl Me—C(O)— HPhenyl H 5.146 3-F Phenyl Me—C(O)— H Phenyl H 5.147 4-F Phenyl Me—C(O)—H Phenyl H 5.148 2-Cl Phenyl Me—C(O)— H Phenyl H 5.149 3-Cl PhenylMe—C(O)— H Phenyl H 5.150 4-Cl Phenyl Me—C(O)— H Phenyl H 5.151 2,4-di-FPhenyl Me—C(O)— H Phenyl H 5.152 3,4-di-F Phenyl Me—C(O)— H Phenyl H5.153 2,3-di-F Phenyl Me—C(O)— H Phenyl H 5.154 2,5-di-F Phenyl Me—C(O)—H Phenyl H 5.155 2,6-di-F Phenyl Me—C(O)— H Phenyl H 5.156 3,5-di-FPhenyl Me—C(O)— H Phenyl H 5.157 H H H H H Me 5.158 2-F H H H H Me 5.1593-F H H H H Me 5.160 4-F H H H H Me 5.161 2-Cl H H H H Me 5.162 3-Cl H HH H Me 5.163 4-Cl H H H H Me 5.164 2,4-di-F H H H H Me 5.165 3,4-di-F HH H H Me 5.166 2,3-di-F H H H H Me 5.167 2,5-di-F H H H H Me 5.1682,6-di-F H H H H Me 5.169 3,5-di-F H H H H Me 5.170 H H Me—C(O)— H H Me5.171 2-F H Me—C(O)— H H Me 5.172 3-F H Me—C(O)— H H Me 5.173 4-F HMe—C(O)— H H Me 5.174 2-Cl H Me—C(O)— H H Me 5.175 3-Cl H Me—C(O)— H HMe 5.176 4-Cl H Me—C(O)— H H Me 5.177 2,4-di-F H Me—C(O)— H H Me 5.1783,4-di-F H Me—C(O)— H H Me 5.179 2,3-di-F H Me—C(O)— H H Me 5.1802,5-di-F H Me—C(O)— H H Me 5.181 2,6-di-F H Me—C(O)— H H Me 5.1823,5-di-F H Me—C(O)— H H Me 5.183 H H (CH₃—CH₂—CH₂)₂CH—C(O)— H H Benzyl(Oil) 5.184 H H H H Me Benzyl

BIOLOGICAL EXAMPLES Arena Test: General Method for TestingVermin-Deterring Substances

This method is carried out in titre plates having 6 wells with across-section of 5 cm each, using a computer-supported video system.Each well of the titre plate is lined with a circular filter paper oranother suitable carrier material. The substance of formula I to betested is dissolved in methanol, acetonitrile or another suitablesolvent, with ultrasound treatment and heating being employed forpoorly-soluble substances. In an amount of 1 to 100 μg/cm², thedissolved test substance is placed in the centre of the filter paper ona quadrant or circular area of ca. 2.4 cm² radius. 4 of the 6 wells arefilled with different test substances or with the same test substance indifferent dilutions (e.g. 1, 3.2, 5, 10 and 20 μg/cm²). The 5th well istreated with DEET (N,N-diethyl-m-toluamide) as standard substance. The6th well is filled with the pure solvent and serves as a control. 60 to100 larvae or 25 to 50 nymphs or 10 to 25 adults of the parasite to betested, e.g. ticks, are added to each filter paper, and the system iscovered with a pane of glass and positioned under a video camera. Atintervals of 5 seconds, the video camera takes individual pictures ofall 6 wells. For a qualitative evaluation, these images are observed ina time-lapse as a continuous film, optically following the movements ofthe parasites on the filter paper and comparing them with the movementsin the control well no. 6 or with the standard in the 5th well. Aqualitative observation is thus made as to whether the test parasitesmove evenly over the whole surface of the filter paper and ignore thetest substance, or whether and over what period they avoid the treatedzone, and what influence the dilution of the test substance has on thebehaviour of the test parasites. In this way, neutral and deterringsubstances are determined. At the same time, the duration of activity ofthe test substance is determined and compared with that of the standard.By plotting all the images for each individual well over one another,different areas of density are obtained. This represents the frequencyat which the parasites visit certain places. This frequency is evaluatedstatistically and thus quantitatively by the Willcoxon method in acomparison with the control and with the standard. Compounds of Tables1, 2, 3, 4, and 5 are tested according to this protocol with variousparasites, for example the compounds Nos. 1.001, 2.001, 3.001, 4.001,5.001, 5.184, 5.185, and 5.186 display excellent activity.

Arena Test In Vitro Against Amblyomma Hebraeum or Variegatum (Nymphs)

The test is carried out as described above, with ca. 25 to 50 nymphsbeing added per well. 10 mg of dissolved test substance is applied to anarea of 2.4 cm² radius. An evaluation of the video images shows that thecompounds of formula I display marked deterrent action against Amblyommanymphs, which lasts considerably longer than that of DEET. Particularlymarked long-term activity is shown for example by using the compoundsNos. 1.001, 2.001, 3.001, 4.001, 5.001, 5.184, 5.185, and 5.186 even upto a dilution of 3.2 μg/cm².

Arena Test In Vitro Against Boophilus Microplus Biarra (Larvae)

The test is carried out as described above, with ca. 60 to 100 larvaebeing added per well. 10 mg of dissolved test substance is applied to anarea of 2.4 cm² radius. An evaluation of the video images shows that thecompounds of formula I display marked deterring action against Bophiluslarvae, which lasts considerably longer than that of DEET. Particularlymarked long-term activity is shown for example by using the compoundsNos. 1.001, 2.001, 3.001, 4.001, 5.001, 5.184, 5.185, and 5.186 even upto a dilution of 10 μg/cm².

Arena Test In Vitro Against Rhipicephalus Sanguineus (Nymphs)

A test is carried out analogously to example B using ca. 40 to 50nymphs. An evaluation of the video images shows that the compoundsaccording to the invention display good deterring action. In particular,the compounds are notable for their almost complete deterring action,which lasts considerably longer than that of DEET. Particularly markedlong-term activity is shown for example by compounds Nos. 1.001, 2.001,3.001, 4.001, 5.001, 5.184, 5.185, and 5.186 even up to a dilution of 10μg/cm².

Analogous tests indicate a long term activity for various species offly, such as Musca domestica.

1. A non-therapeutical process for deterring vermin from warm-bloodedanimals, whereby a compound of formula I

or their acid addition salts, wherein R1 is hydrogen, halogen, NH₂, OH,C₁-C₃-alkyl or C₁-C₃-alkoxy; m is 1, 2 or 3; R2 is hydrogen, halogen,unsubstituted or substituted benzyl, —C(O)—R8, C₁-C₂₀-alkyl,halo-C₁-C₂₀-alkyl, C₂-C₂₀-alkenylalkyl, C₃-C₆-cycloalkyl,C₁-C₂₀-alkoxyalkyl, C₁-C₂₀-hydroxyalkyl, C₁-C₂₀-alkoxy, unsubstituted orsubstituted aryl R3 is a substituent selected from the group consistingof

R4 is hydrogen, C₁-C₂₀-alkyl, benzyl, —C(O)—R8; n is 0 or 1; and R8 isC₁-C₂₀-alkyl, C₁-C₂₀-alkoxy, unsubstituted or substituted aryl,unsubstituted or substituted aryloxy, benzyl; is applied topically,together with a spreading additive, to the skin, the pelt or the plumageof the warm-blooded animal.
 2. Process according to claim 1, whereby thecompound of formula I is a compound of the formula Ia or one of its acidaddition salts

wherein R1, R2 and R4 are as defined as in claim
 1. 3. Process accordingto claim 2, wherein R1 is hydrogen or halogen; m is 1 or 2, R2 ishydrogen, C₁-C₃-alkyl, or phenyl; and R4 is hydrogen or acetyl. 4.Process according to claim 1, whereby the compound of formula I is acompound of the formula Ib or one of its acid addition salts

wherein R1, R2, R4 and m have the meanings specified under formula I. 5.Process according to claim 4, wherein R1 is hydrogen or halogen; m is 1or 2, R2 is hydrogen, C₁-C₃-alkyl, or phenyl; and R4 is hydrogen oracetyl.
 6. Process according to claim 1, whereby the compound of formulaI is a compound of the formula Ic or one of its acid addition salts

wherein R1, R2, R4 and m have the meanings specified under formula I. 7.Process according to claim 6, wherein R1 is hydrogen or halogen; m is 1or 2, R2 is hydrogen, C₁-C₃-alkyl, or phenyl; and R4 is hydrogen oracetyl.
 8. Process according to claim 1, whereby the compound of formulaI is a compound of the formula Id or one of its acid addition salts

wherein R1, R2, R4 and m have the meanings specified under formula I. 9.Process according to claim 8, wherein R1 is hydrogen or halogen; m is 1or 2, R2 is hydrogen, C₁-C₃-alkyl, or phenyl; and R4 is hydrogen oracetyl. 10-12. (canceled)
 13. Process according to claim 1 whereby thecompound of formula I is applied in the form of a pour-on or spot-onformulation.
 14. Process for deterring vermin from places or materialswhere they are not wanted, whereby an effective amount of a compound offormula I according to claim 1 is applied to the place or to thematerial, at which one would like to deter insect pests, tics or mites.15. Composition for repelling vermin, comprising a compound of formula Iaccording to claim 1 and a spreading additive.
 16. Process for thepreparation of a composition for repelling vermin, whereby a compound offormula I according to claim 1 is mixed with a spreading additive.17-18. (canceled)